Our laboratory is exploring ways to increase energy expenditure to combat obesity and metabolic syndrome by studying stem cells and signaling pathways that give rise to adipose tissue. There are several types of adipose tissue. Chronic periods of overeating result in weight gain due to excess energy being stored as fats in white adipose tissue. Accumulation of white adipose tissue in overweight individuals correlates with metabolic syndrome and disease. Brown adipose tissue plays the opposite role by converting energy stored in fats to heat. Brown adipose tissue plays a role in keeping infants and other mammals warm through a process known as non-shivering thermogenesis, which is activated when the sympathetic nervous system senses cold exposure. Studies have found that the activity of brown adipose tissue in both humans and rodents correlates positively with reduced risk of metabolic syndrome, making it an attractive tissue to develop obesity therapies. To take advantage of the potential therapeutic properties of brown adipose tissue, we are developing both mouse and human models to study brown adipose development and activation. Examples of projects include:

Modulation of TGF-beta and BMP signaling pathways to activate or increase the size of brown adipose tissue

Studies of transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) signaling in mice have shown that these pathways are important for the development and activation of brown adipose. We are creating mouse models to target specific genes that give rise to key signaling components found in these pathways in an attempt to identify therapeutic targets that can enhance brown adipose function. These genetic studies will lead to the generation of therapeutic compounds that can be used to increase energy expenditure and decrease weight gain.

Generation of human brown adipose tissue from pluripotent stem cells for the treatment of metabolic syndrome

One obstacle in the study of brown adipose tissue development in humans has been the difficulty of procuring adult and early stage embryonic and fetal tissues. To solve this problem, we are developing cell culture methods to generate a renewable source of brown adipocyte specific stem cells from induced pluripotent stem cells (iPS cells). Direct reprogramming of somatic cells into iPS cells resets them to an early embryonic stem cell-like state and also raises the possibility of producing patient-matched cells for the study and treatment of obesity. Using these models, we are attempting to determine how brown adipose develops in humans and how this tissue can be therapeutically activated. This includes the study of both of TGFB and BMP signaling pathways and how they contribute toward the development of human brown adipose. Using immunodeficient mice, we are also exploring ways to determine if human iPS-generated brown adipose can be transplanted directly in animals in an attempt to see if it can serve directly as a therapeutic tissue to increase energy expenditure and combat metabolic syndrome.